8-hydroxyquinolinium di-hydrogen phosphate and method of preparation



. B-hydroxyquinoline is Patented Aug. 5, 1952 UNITED STATES TENT orice 8-HYDROXYQUINOLINIUM DI-HYDROGEN PHOSPHATE AND METHOD OF PREP- ARATION Nathaniel Grier, Brooklyn, N. Y., and Charles Casalbore, Passaic, N. J., as'signors to Dar-Syn Laboratories, Inc., Hawthorne, N. 5., a corporation of New Jersey No Drawing. Application October 17, 1950,

- Serial No. 190,660

'8 Claims. (01. 260-286) will react to form either the acid sulphate or the neutral sulphate. In the case of phosphoric acid,

I salts with the 8-hydroxyquinoline have been described in the literature.

Such salts were triquinolinium phosphate and diquinolinium monosodium phosphate. However, the prior art has not described the monoquinclinium phosphate.

It is among the objectsof the present invention to provide a process for producing the quinolinium di-hydrogen phosphate which is simple and highly efficient.

It is also among the objectsof the present invention to provide a reaction product which is relatively pure and is adapted for various commercial uses.

The invention is based on the discovery that 8- hydroxyquinoline will react with phosphoric acid to form the monoquinolinium phosphate regardless of the molar ratio of the reactants, provided that the reaction is conducted in the presence of weak acids or weakly acidic substances, the ionization constants, Ka, of which are 10- or lower.

Phosphoric acid dissociates as follows:

The following are specific examples of procedures for producing the compound:

Example I 14.5 gms. (0.100 mol) 8-hydroxyquinoline is dissolved in 50 c. c. warm glacial acetic acid. No heat is necessary for the reaction and the warm acid merely facilitates the solution. To this is added with stirring 12 gms. (0.104 mol) 85% phosphoric acid. The conditions are sub stantially anhydrous and the reaction takes place at room temperatures, namely, from about 18 acid and dried. A good yield is obtainedfblng about 22.5 grams. The melting point of the product is 185 to 187 C. The reaction is as For analysis a sample of the above'prepared mono S-hydroXyquinolinium di-hydro'gen phosphate was dissolved-in twice its weight of water, the pH adjusted carefully to 7 using dilutesodium hydroxide. The resultant'mixturefwassubjected to steam distillation until no evidence of S-hydroxyquinolinetvas found in the-distillate. The residue which-consisted of only the 'phosphate saltwas analyzed in the usual manner for 20 phosphate.

CQH'ION' Til- 3P0 Y Per cent Theoretical, HaPOr 40.33 I 40.25 Found, HzPO4 {40.38

to 24 C. During the stirring a yellow precipitate is rapidly formed with the evolution of heat due to salt formation. The reaction mixture is cooled to room temperature and the product is separated from the solution by suction filtration. It

is washed with a small amount of glacial acetic 1 The product is a crystalline yellow salt,'more than 33% soluble in water at room temperature,- weight/volume, and gives a weakly acidic solution inwater. g

' Example II phosphoric acid originally added was precipi-' tated as the mono B-hydroxyquinolinium di-hydrogen phosphate. Analysis of the productzconfirmed this. Example III 14.5 g. (0.10 mol) S-hydroxyquinoline were dissolved in 50 c. c. propionicacid with the formation of an orange color. To this with cooling there were added 12 gms. phosphoric acid. Immediate precipitation resulted. On further cooling and rubbing the product became granular. It was removed by suction-filtration,

washed with a small amount of propionic acid,

Example IV 14.5 g. (0.10 mol) 8-hydroxyquinoline were dissolved at room temperature in 75 c. c. ethyl acetoacetate (enol form is weakly ,acidic) with the formation of a yellow solution. -A ddition:.gf 12 gms. 85% phosphoric acidcaused the form tion of a gummy precipitate. On cooling and rubbing a granular product was obtained. After suctionfiltration, washing with ethyl -acetoacetate followed by ether gave a final yield of 21--.5 gms.

8-hydroxyquinolinium di-hydrogen phosphate after drying. Recrystallization from 96 alcohol .car rrystals, .M.- E' ..-.1 l87 c.

iii-sample V 14.5 g. (0.10 mol) 8-hydroxyquinoline weLe.,.di s solved by heating in 50 c. c. meta cresol. With cooling L2,gms."85.% phosphoric acid were added. A supersaturated solution resulted. ,This was seeded :with 8-hydroxyquinolinium dij-hydrogen phosphate and. cooled until complete precipitation resulted. The heavy moss was rubbed with ,an equal volume of ether and suctionefiltered. It

was thoroughly ether washed and dried. 24 gms.

, ,procedureincthat theprocess is ,simpleto conduct mequ rinano :sne alh at ns or qu n T yield of pure product is high, being. atleast 130%, and the mother liquonmay. be re-used for further reaction. Therefore, practically theoretical yields may eventually be obtained in commercial practice. This process is-of especial valuewhen the quantity of 8-hydroxyquinoline originally present is-unknown. By reactioninsuch-weakly acidic solvents-e. g.-- glacial acetic acid, -8=hydroxyquino- "line will formonly one product,- mono-8-hydroxyquinolinium -di+hydrogen phosphate, independof --which component is present in :molar excess.

Inthe-above examples, the media .were nonaqueous. But it is possible to operatethe process in *the presence of water. For instance, .the

"- proo'essof Examples 1 or 2 may be conducted -with-aqueous acetic acid,: the monosalt. formed in the reaction remaining solution. -It may be recovered by-evaporation of water, by the use of a solvent miscible with acetic acid and. water .such as acetone, by extracting the water as by the use of methyl ethyl ketone, and by other known expedients, The phosphoric acid-may be in excess --mols-thereof-to'1 mol -of8-hydroxyquinoline, the

"salt formed-precipitating from the solution. The warden of addition ofthe-reactants maybe different-from-that described in the examples.

*These and other changes may be made in the 'detailspfthe invention, which is to be broadly construed. and to be limited only'by the'character of the claims appended hereto.

We claim:

1. A method of making mono 8-hydroxyquinolinium dirhydrogen phosphate which comiprises; dissolving 8-hydroxyquinoline in a weakly acidic solventyhaving an ionization constant of not over 10 and mixing phosphoric acid there- "withrwhereby said mono phosphate is formed.

'12. A method of making mono 8-hydroxy- .quinolinium ,di -hy drogen phosphate which comprises dissolving 8-hydroxyquinoline in a weakly :acidic solvent'having an ionization constant of not over 10- and mixing phosphoric acid therewith, -whereby said mono phosphate is formed and is precipitated, and separating the precipitate from the remaining liquid.

'3. ;A-method of making mono -8hydroxyquinolinium di-hydrogen phosphate whichcomprises dissolving-8-hydroxyquinoline in a weakly acidicsolvent having an ionization constant of not over -10* and mixing phosphoric acid therewith, whereby said mono phosphate is formed and is precipitated, said solution being substantially anhydrous,'andseparating the precipitate from the'remaining liquid.

4. -A method of making mono 8-hydroxyquinolinium di-hydrogen phosphate which comprisesdissolving S-hydroxyquinoline in a weakly .acidic solvent having'an ionization constant of not over 10- and mixing phosphoric acid therewith, whereby said monophosphate is formed, the-reactants being in substantially equimolecular proportions.

-5. 'A method of making mono -8-hydroxyquinolinium di-hydrogen phosphate which comprises-dissolving -8-hydroxyquinoline in a weakly acidic "SOIVGHt'haViIig-an ionization constant of not over 10 and mixing-phosphoric acid therewith, whereby said mono phosphate is formed, causing-saidphosphateto precipitate, cooling the -mixtureto room temperature, and separating the precipitate from the remaining liquid.

6. A method of making mono -8-hydroxyquinolinium di-hydrogen phosphate which comprises dissolving B-hydroxyquinoline in glacial acetic acid, mixing therewith an approximately equimolecular' quantity of phosphoric acid, whereby said product is precipitated, and separating said product from the remaining liquid, said-product being substantially pure 8-hydroxyquinolinium di-hydrogen phosphate.

7. A method of 'making mono B-hydroxyquinolinium di;-hydrogen phosphate which comprises dissolving 8-hydroxyquinoline in a weakly acidic solvent having an ionization constant of not over 10 and mixing phosphoric acid therewith, said-mixture being substantially free from bases stronger than 8-hydroxyquinoline, whereby said mono phosphate is formed.

\ 8. A composition of matter which is mono 8- hydroxyquinolinium di-hydrogen phosphate having the following structural formula:

I H21 Or O\1 Y/. H and having a. slightly acid reaction.

NATHANIEL GRIER. CHARLES CASALBORE.

Noreferences cited. 

6. A METHOD OF MAKING MONO 8-HYDROXYQUINOLINIUM DI-HYDROGEN PHOSPHATE WHICH COMPRISES DISSOLVING 8-HYDROXYQUINOLINE IN GLACIAL ACETIC ACID, MIXING THEREWITH AN APPROXIMATELY EQUIMOLECULAR QUANTITY OF PHOSPHORIC ACID, WHEREBY SAID PRODUCT IS PRECIPITATED, AND SEPARATING SAID PRODUCT FROM THE REMAINING LIQUID, SAID PRODUCT BEING SUBSTANTIALLY PURE 8-HYDROXYQUINOLINIUM DI-HYDROGEN PHOSPHATE. 